360. Breakthrough Invasive Pulmonary Aspergillosis During Isavuconazole Prophylaxis in Patients with Hematologic Malignancies: A Single-Center Experience

BACKGROUND: Isavuconazole (ISA) is an attractive candidate for prophylaxis against invasive mould infections (IMIs) due to its broad-spectrum activity, ease of dosing, favorable side-effect profile, and limited drug–drug interactions. Clinical experience using ISA prophylaxis in high-risk patients is lacking. We describe our experience using ISA as first-line primary prophylaxis in select patients with hematologic malignancies and hematopoietic cell transplant (HCT) recipients over a 13-month period. METHODS: We conducted a retrospective review of adults with hematologic malignancies and HCT recipients who received ≥7 days of uninterrupted ISA primary prophylaxis between September 1, 2016 and September 31, 2017. Breakthrough IMIs were documented through chart review and classified as probable or proven according to standard criteria. The study was approved by the OHSU IRB. RESULTS: A total of 135 patients received 184 courses of ISA prophylaxis for AML (N = 100), GVHD (N = 36), “high-risk HCT” (≥14 days neutropenia immediately prior to HCT; N = 25), and other indications (N = 23). Ten cases of proven/probable breakthrough IMIs were identified (invasive pulmonary Aspergillosis (IPA) = 6, Mucorales = 2, Fusarium = 2). Four cases of breakthrough IPA occurred during prophylaxis for AML, and two occurred during prophylaxis after high-risk HCT. All breakthrough IPA occurred during prolonged neutropenia (median 46 days, range 16–181). The median duration of ISA prophylaxis prior to breakthrough IPA was 15 days (range 10–37). The median serum ISA trough level at breakthrough IPA was 3.7 μg/mL (range 3.1–6.3). During this same time period, there was no breakthrough IPA during 101 courses of voriconazole or posaconazole (POS) prophylaxis in similar patients. Only one case of breakthrough IPA occurred during 244 courses of POS prophylaxis in the 18 months prior to the introduction of ISA prophylaxis. Due to the higher than expected rate of breakthrough IPA, POS replaced ISA as first-line primary prophylaxis in October 2017. Since then there have been no cases of breakthrough IPA on POS prophylaxis. CONCLUSION: Our institutional experience indicates that additional studies are needed to determine the role of ISA for prophylaxis in certain high-risk hematologic malignancy patients. DISCLOSURES: J. S. Lewis II, Merck: Consultant, Consulting fee